Obesity and insulin sensitivity effects on cardiovascular risk factors: Comparisons of obese dysglycemic youth and adults

Abstract

Background: Obesity and pubertal insulin resistance worsen cardiovascular (CV) risk factors in youth. It is unclear how the relationships of obesity and insulin resistance with CV risk compare to adults.

Subjects and methods: We evaluated 66 pubertal youth (mean ± SD: age 14.2 ± 2.0 years, body mass index [BMI] 36.6 ± 6.0 kg/m2 , hemoglobin A1c [HbA1c] 38.5 ± 6.1 mmol/mol) and 355 adults with comparable BMI (age 52.7 ± 9.4 years, BMI 35.1 ± 5.1 kg/m2 , HbA1c 39.8 ± 4.2 mmol/mol) participating in a multicenter study. Insulin sensitivity was quantified using hyperglycemic clamps. Assessment of CV risk factors was standardized across sites. Regression analyses compared the impact of insulin sensitivity and CV risk factors between youth and adults.

Results: Obese pubertal youth were more insulin resistant than comparably obese adults (P < .001), but with similar slopes for the inverse relationship between insulin sensitivity and obesity. The impact of obesity on CV risk factors was explained by insulin sensitivity (P = NS after adjustment for sensitivity). The two age groups did not differ in relationships between insulin sensitivity and diastolic blood pressure, total cholesterol, and low-density lipoprotein (LDL) cholesterol, after adjusting for obesity. However, while systolic blood pressure (SBP) and high-density lipoprotein (HDL) cholesterol exhibited the expected direct and inverse relationships, respectively with insulin sensitivity in adults, these slopes were flat in youth across the range of insulin sensitivity (P ≤ .05 for group differences).

Conclusions: Effects of obesity on CV risk factors were attributable to insulin sensitivity in both groups. The relationships between insulin sensitivity and CV risk factors were similar in obese youth and adult groups except for SBP and HDL cholesterol.

Clinical trial registration: The RISE consortium studies are registered through Clinicaltrials.gov as NCT01779362 (Adult Medication Study); NCT01763346 (Adult Surgery Study); and NCT01779375 (Pediatric Medication Study). Clinical trial registration numbers: NCT01779362, NCT01779375 and NCT01763346 at clinicaltrials.gov.

Keywords: adult; cardiovascular risk; insulin resistance; obesity; youth.

Conflict of interest statement

Duality of Interest: K.J.M. holds an investigator-initiated research grant from Novo Nordisk. S.A.A. and S.E.K. serve as paid consultants on advisory boards for Novo Nordisk. S.A.A is a participant in a Novo Nordisk sponsored clinical trial. T.A.B. has received research support from Allergan Corporation and Apollo Endosurgery. No other potential conflicts of interest relevant to this article were reported.

© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Figures

Figure 1.

Relationship of insulin sensitivity to BMI (Panel A), to waist/hip ratio (panel B) and waist/height ratio (panel C). Youth are presented in red and adults in blue. Insulin sensitivity (M/I, the clamp glucose disposal rate divided by the steady-state insulin concentration) is presented on a log scale. The slopes relating insulin sensitivity to obesity measures were all significant (p

Figure 2.

Body Mass Index and Insulin Sensitivity as Determinants of CV Risk Factors in Youth and Adults. Youth are presented in red and adults in blue. Insulin sensitivity (M/I, the clamp glucose disposal rate divided by the steady-state insulin concentration) and triglycerides are presented on a log scale. The underlying statistical analyses are presented in Table 2. The slopes were significantly different between age groups only for M/I versus HDL cholesterol (p=0.014); M/I versus SBP approached but did not reach significance (p=0.053). BMI, body mass index; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; SBP, systolic blood pressure.